突变型异柠檬酸脱氢酶抑制剂的临床研究进展

异柠檬酸脱氢酶(Isocitrate Dehydrogenase,IDH)是参与三羧酸循环的关键代谢酶,催化异柠檬酸氧化脱羧为α-酮戊二酸(α-KG)。异柠檬酸脱氢酶突变被证实是驱动肿瘤发生的机制之一。IDH突变常发生在酶活性位点,突变发生后会改变酶的功能,从而催化肿瘤代谢产物D-2-羟戊二酸(D-2-HG)生成积累,导致细胞表观遗传异常,阻断正常细胞分化,进而促进肿瘤发生。因此,靶向抑制突变型异柠檬酸脱氢酶,是一种有效的肿瘤治疗策略。目前,FDA已批准靶向抑制突变型异柠檬酸脱氢酶1(mIDH1)的Ivosidenib、Olutasidenib以及靶向抑制异柠檬酸脱氢酶2(mIDH2)的Enasidenib用于治疗带有IDH突变的急性髓系白血病(AML)。本文主要讨论了突变型异柠檬酸脱氢酶抑制剂目前临床的研究进展,为开展突变型异柠檬酸脱氢酶抑制剂研究工作提供参考。

异色瓢虫十九斑变型对菜蚜的捕食功能研究

[目的]为优势种异色瓢虫十九斑变型的保护利用和菜蚜的生物防治提供理论依据。[方法]以甘蓝田异色瓢虫十九斑变型的各龄幼虫及成虫为供试虫源,设5个菜蚜密度,研究异色瓢虫十九斑变型对菜蚜的捕食功能反应。[结果]不同虫态的异色瓢虫十九斑变型对菜蚜的日捕食量差异较大,当菜蚜密度相同时,4龄幼虫捕食量最大,成虫和3龄幼虫次之,各龄幼虫及成虫对菜蚜的捕食功能反应均可以用HollingII型圆盘方程拟合。同一虫态瓢虫的捕食量随着蚜虫密度的增大而相应增大。异色瓢虫十九斑变型各龄幼虫及成虫自身密度对捕食作用的干扰效应明显,符合Hassel-Verley的干扰效应模型。[结论]不同虫态的异色瓢虫十九斑变型对菜蚜的日捕食量差异较大,且随捕食者自身密度的增加而减少。

变异型心绞痛

变异型心绞痛那开宪１０００５０北京友谊医院［编者按］在内科临床工作中，常常会碰到各种实际问题或疑难问题需要解答。为满足广大基层医务人员的需要，本刊特开辟此专栏。欢迎广大基层医务工作者踊跃来信，提出在临床工作中需要解答的问题，我们将请有丰富临床经验的有...

Genetic Structure of the Oriental River Prawn (Macrobrachium nipponense) from the Yangtze and Lancang Rivers, Inferred from COI Gene Sequence

This study analyzed nueleotide sequences from the mitochondrial eytochrome oxidase submit （COI） gene region （450 bp） to investigate the genetic structure of the oriental river prawn （ Macrobrachium nipponense ） among nine populations from the Yangtze and Lancang Rivers. A total of 79 individuals were collected for this work. Eighty-nine nucleotides were found to be variable, resulting in 46 haplotypes. Among the nine populations, the population from Kunming shows the greatest level of variability （h = 1.000, π = 0.028）, whereas the population from Cbongqing exhibits the lowest level of variability （h = 0.700,π = 0.008）. Analysis of molecular variance suggested that of the total genetic diversity, 9.66% was attributable to inter-population diversity and the remainder （90.34%） to differences within populations. A molecular phylogenetic tree constructed using the Neighbor-joining （N J） method showed that the 46 haplotypes were assigned to two clades associated with geographic regions. These results provide basic information for the conservation and sustainable exploitation of this species.

Variance Type of Capsule Morphological Characters in Platycodon grandiflorum Population

[ Objective] The aim was to study variance type of capsule morphological characters in Platycodon grandiflorum population, and provide some theoretical basis for seeking to genetic markers which can differentiate different P. grandiflorum and breeding new varieties. [ Method] According to shape morphological characters of capsule from the same population of perennial purple P. gandiflorum, seven types of distinct di- versity capsule were selected, variance analysis and multiple comparison on the length, diameter, length/diameter of the different types of capsule were carried out. [ Result] There is unicolor and bicolor, even trichrome, among main color was brown and purple. Capsule shape was main cone, furthermore, containing long roller type, spheroidicity and sphericity. [ Conclusion] P. gandiflorum capsule was divided into long form, short form and middle type from length/diameter size in perennial culture P. gandiflorum population.

Research on Phenotypic Diversity of Different Populations of Leymus Chinensis in Zhalong Wetlands

[Objective] This paper aimed at revealing the rules of phenotypic variation of Leymus chinensis in Zhalong wetlands and providing the scientific and theoretical bases for devising protection strategies of Leymus chinensis populations in Zhalong National Nature Reserve.[Method] Four phenotypic traits of five Leymus chinensis populations in Zhalong Wetlands were comparison and analysis using principal component analysis method and UPGMA cluster analysis method.[Result] There were significant differences among the four phenotypic traits of five populations,the order of coefficients of variation were node number〉plant height〉leaf width〉leaf length;the order of variation degrees of the populations from large to small was KQH,MD,JZ,ZK,TTG population.Results of principal component analysis suggested that the four traits were all factors led to the phenotypic differences among the populations of Leymus chinensis.Leymus chinensis of five populations were divided into three groups by cluster analysis,MD,JZ and TTG were classified as one group,KQH and ZK population were individually classified as one group.[Conclusion] Leymus chinensis had large-scale phenotypic variations and showed strong adaptability to different habitats,which was very important for selection,breeding of fine varieties and germplasm conservation.

Effects of Soil and Environment on Quality Traits of Purple-fleshed Sweetpotato

For the study of main traits of purple-flashed sweetpotato in different soil and ecological environments, 18 cultivars of purple-flashed sweetpotato with different enthocyenin contents were planted at Yancheng and Xuzhou separately. The main quality traits were determined. The results showed the quality traits of purple-fleshed sweetpotato were significantly influenced by soil and ecological environments. Geno- type （G）, environment （E） and genotype x environment （GxE） interaction had signif- icantiy effects on the contents of anthocyanin, dry matter, starch, protein, reducing sugar and soluble sugar in storage roots. Anthocyanin content was most easily af- fected by the environment. The E effect on anthocyanin content was greater than G and GxE effects. However, the GxE interaction effects on other 5 quality traits were greater than G and E effects. The 6 quality traits were significantly different at 1% level under different environments respectively. The contents of dry matter, starch and anthocyenin were higher in Yancheng than in Xuzhou, while the contents of protein, reducing sugar and soluble sugar were higher in Xuzhou. The variation co- efficients of all quality traits at Yancheng and Xuzhou were in the same order： an- sugar〉protein〉starch, the variation coefficient of anthocyanin content was higher in Xuzhou, and the variation coefficients of other 5 traits were higher in Yancheng. Correlation analysis showed that the reducing sugar and solu- ble sugar contents were negatively correlated with starch content, and had no sig- nifiant correlation with anthocyanin and protein contents. Dry matter content and starch content were positively correlated, and anthocyanin content and other quality traits had no significant correlation.

长链非编码RNA在肝纤维化发生发展中的作用研究进展

肝纤维化是指肝细胞外基质的弥漫性过度沉积与异常分布,是肝脏对慢性损伤的病理性修复反应,肝星状细胞(HSCs)的激活是其发生的重要环节。非编码RNA(ncRNA)已成为细胞信号传导和相关人类疾病的重要调节因子,长链非编码RNA(lncRNA)是一类长度超过200个核苷酸的ncRNA,过去认为其不具备蛋白编码能力,近年认为其可通过编码小肽调控细胞增殖。lncRNA参与各种器官的纤维化,包括肝脏、心脏、肺和肾脏。在肝纤维化过程中,lncRNA参与调节多种细胞生物学过程,根据作用可分为三类。大部分lncRNA发挥肝纤维化促进作用,如肺腺癌转移相关转录本1、肝纤维化相关的lncRNA1、浆细胞瘤变型异位因子1等;少部分lncRNA发挥抑制作用,如母系表达基因3、生长停滞特异转录因5等;极少数lncRNA具备促进和抑制肝纤维化发生的双重作用。

Physiological Analysis of Two Arabidopsis thaliana Mutants in Response to CO2

[Objective] The 15urpose was to seek for the different phenotypes between wild type and Arabidopsis Mutants in response to CO2. [Method] The epidermis bioassays and seed germination test were carried out to analyze the physiological characteristics of two Arabidopsis mu- tants and their wild type. [Result] There existed distinct differences in stomata apertures, water loss and leaf temperature compared with wild type except for stomata density. In addition, seed germination test on the medium indicated that cdfl was insensitive to ABA, mannitol and NaCI, but cdsl performed contrary to cdil. [ Conclusion] There are some different physiological characteristics between wild type and mutants.

Genetic Variation of Porcine Circovirus Type 2 Isolate 201105ZJ

[Objective] This study aimed to investigate the genetic variation of porcine circovirus type 2 （PCV2） in China. [Method] The strain was isolated from infected samples by cel passage and preliminarily identified by PCR and IFA. Ful-length genome of the isolated strain was obtained by specific amplification for homology and phylogenetic analysis. [Result] A PCV2 strain was successful y isolated and named 201105ZJ, which could proliferate in PK15 cel lines. Specific fragments could be amplified by specific PCR assay. According to results of IFA assay, specif-ic immunofluorescence was observed; the TCID50 was low （102.67）; the ful-length genome sequence of the isolated strain was 1 768 bp, sharing 94.1%-96.8% ho-mology with 13 reference strains; to be specific, the isolated strain exhibited the highest homology of 96.8% with AF055392PCV2a; the isolated strain 201105ZJ and reference strain AF055392 belonged to genotype PCV2a, exhibiting a distant genetic relationship with genotype PCV2c. [Conclusion] Characteristics of genetic variation of PCV2 isolate 201105ZJ provided theoretical basis for vaccine development, investi-gation of PCV2 pathogenesis, and prevention and control of porcine circovirus-as-sociated diseases （PCVAD） in East China.

Genetic Variation and Differentiation of Larix decidua Populations in Swiss Alps

Genetic diversity within and among six subpopulations of Larix decidua Mill. from two altitudinal transects of Swiss Alps was investigated using 6 enzyme systems coding for 8 loci. Globally, the mean proportion of polymorphic loci was 22.9%, the average number of alleles per locus was 1.3, and the mean expected heterozygosity was 0.095. Only 5.8% of the genetic variation resided among populations. The mean genetic distance was 0.006. Several significant differences of gene frequencies were found between different age classes. Positive values of the species mean fixation index observed in this study suggested a considerable deficit of heterozygotes in the populations of L. decidua of Swiss Alps. At one of the sites (Arpette), the highest subpopulation in elevation gave the lowest level of genetic diversity (as evidenced by the lowest proportion of polymorphic loci and the lowest mean expected heterozygosity) and the largest value of genetic distance when compared to other subpopulations. The genetic differences between the highest subpopulation and the other ones suggest that the founder effect may be an important factor influencing genetic differentiation of L. decidua populations at Arpette transect.

Hapseeker:A C++ Program for Analyzing Haplotype

The C++ program: Hapseeker was developed to analyze DNA or RNA sequence, besides, Hapseeker could be used to identify haplotype, calculate frequency of each haplotype as well as find variable site quickly. Moreover, Hapseeker had many advantages such as simple operation, rapid running speed and high accuracy.

Genetic Variation Among White Croaker Populations

To investigate the genetic structures and differentiation of different wild populations of white croaker （Pennahia argentara）, horizontal starch gel electrophoresis was performed on 133 individuals collected from five different locations in China and Japan. The eleven enzyme systems revealed 15 loci, of which eleven were polymorphic. The percentage ofpolymorphic loci of white croaker populations varied from 6.67% to 53.3.3%; the mean observed and expected heterozygosity ranged from 0.0033 to 0.0133 and 0.0032 to 0.0191, respectively. The expected heterozygosity revealed a low genetic variability for white croaker in comparison with other marine fishes. The genetic distances between populations ranged from 0.00005 to 0.00026. A weak differentiation was observed within each clade and between clades; and no significant differences in gene frequencies among populations were observed in white croaker. Among the five populations, three Chinese populations showed more genetic diversity than that in Japanese populations.

Genetic interactions and modifi er genes in Hirschsprung's disease

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

Spatiotemporal interpolation of precipitation across Xinjiang, China using space-time CoKriging

In various environmental studies, geoscience variables not only have the characteristics of time and space, but also are influenced by other variables. Multivariate spatiotemporal variables can improve the accuracy of spatiotemporal estimation. Taking the monthly mean ground observation data of the period 1960–2013 precipitation in the Xinjiang Uygur Autonomous Region, China, the spatiotemporal distribution from January to December in 2013 was respectively estimated by space-time Kriging and space-time CoKriging. Modeling spatiotemporal direct variograms and a cross variogram was a key step in space-time CoKriging. Taking the monthly mean air relative humidity of the same site at the same time as the covariates, the spatiotemporal direct variograms and the spatiotemporal cross variogram of the monthly mean precipitation for the period 1960–2013 were modeled. The experimental results show that the space-time CoKriging reduces the mean square error by 31.46% compared with the space-time ordinary Kriging. The correlation coefficient between the estimated values and the observed values of the space-time CoKriging is 5.07% higher than the one of the space-time ordinary Kriging. Therefore, a space-time CoKriging interpolation with air humidity as a covariate improves the interpolation accuracy.

Genetic variation of natural and cultured stocks of Paralichthys olivaceus by allozyme and RAPD

Population genetics of the left-eyed flounder, Paralichthys olivaceus, including natural and cultured stocks distributed in the coastal waters near Qingdao of eastern maritime China, was analyzed in allozyme and RAPD. The results showed that among total 29 gene loci of 15 isozymes, 9 and 7 were po- lymorphic in natural and cultured stocks, respectively. The status of genetic diversity in P. olivaceus is low in terms of polymorphic loci in chi-square test and genetic departure index of Hardy-Weinberg equi- librium. More alleles in IDHP, CAT, GDH and Ldh-C allozymes were found in the fish, which could be used as markers in assortive breeding and distinguishing stock, population or species evolution. Total 88 and 86 RAPD bands ranging from 200 to 2 500 bp were recognized individually in average of 7.8–8.0 bands per primer. The genetic diversity in cultured stock is lower than that in natural ones showing an ob- viously decreasing genetic divergence. Therefore, effective countermeasures must be taken to protect ge- netic resources of marine cultured fishes. The 2 markers have their own pros and cons. Combining the 2 markers to investigate the genetic variation of populations is suggested. The results provide basic data of this flounder and they are useful for studying genetic improvement and genetic resources of the fish.

A spectral mixture model analysis of the Kuroshio variability and the water exchange between the Kuroshio and the East China Sea

For understanding more about the water exchange between the Kuroshio and the East China Sea,We studied the variability of the Kuroshio in the East China Sea(ECS) in the period of 1991 to 2008 using a three-dimensional circulation model,and calculated Kuroshio onshore volume transport in the ECS at the minimum of 0.48 Sv(1 Sv ;106 m3/s) in summer and the maximum of 1.69 Sv in winter.Based on the data of WOA05 and NCEP,The modeled result indicates that the Kuroshio transport east of Taiwan Island decreased since 2000.Lateral movements tended to be stronger at two ends of the Kuroshio in the ECS than that of the middle segment.In addition,we applied a spectral mixture model(SMM) to determine the exchange zone between the Kuroshio and the shelf water of the ECS.The result reveals a significantly negative correlation(coefficient of-0.78) between the area of exchange zone and the Kuroshio onshore transport at 200 m isobath in the ECS.This conclusion brings a new view for the water exchange between the Kuroshio and the East China Sea.Additional to annual and semi-annual signals,intra-seasonal signal of probably the Pacific origin may trigger the events of Kuroshio intrusion and exchange in the ECS.

High Phenotypic Variation in Morus alba L. along an Altitudinal Gradient in the Indian Trans-Himalaya

Ten quantitative morphological characters were studied in 56 Morus alba L. trees representing three natural populations from the trans-Himalayan Ladakh region. The altitude of collection sites ranged from 2815 to 3177 m above the sea level(asl). Coefficient of variation(CV) showed high phenotypic variation in M. alba. Linear regression analysis revealed that leaf and fruit size decreases with an increase in altitude. High CV was observed for leaf length, leaf width, petiole length, leaf area, internodal distance, number of nodes, bud length, fruit length, fruit width and fruit weight. Similarly, a high phenotypic plasticity index was observed for bud length, leaf length, leaf width, petiole length, leaf area, inter-nodal distance, number of nodes, fruit length, fruit width and fruit weight. For every 100 m increase in altitude, leaf length, leaf width and leaf area decreased by 1 cm, 0.8 cm and 16.6 cm2, respectively. Analysis of covariance showed a predominant altitudinal effect on the morphological characters in comparison to the population effect. A small change in the altitude caused significant change in the plant morphological characteristics. The present investigation represents to our knowledge the first study addressing phenotypic variation in mulberryalong an altitudinal gradient.

Modeling Surgery: A New Way Toward Understanding Earth Climate Variability

A new modeling concept, referred to as Modeling Surgery, has been recently developed at University of Wisconsin-Madison. It is specifically designed to diagnose coupled feedbacks between different climate components as well as climatic teleconnections within a specific component through systematically modifying the coupling configurations and teleconnective pathways. It thus provides a powerful means for identifying the causes and mechanisms of low-frequency variability in the Earth's climate system. In this paper, we will give a short review of our recent progress in this new area.